Conventional assessment of severity of airway diseases, including asthma, consists of measures of pulmonary mechanics which are effort dependent and thus not suitable for many pediatric patients, mechanically ventilated patients, or patients with neuromuscular disease. See Crapo R., Pulmonary-function testing. N. Engl. J. Med., 331; 1:25-30; 1994; and American Thoracic Society/European Respiratory Society: Respiratory mechanics in infants--physiologic evaluation in health and disease, Am. Rev. Respir. Dis., 1993; 147:474-96. Currently the Peak Expiratory flow meter is the only method commonly available for home use by asthmatics to monitor the state of their airway disease. This test suffers from being an insensitive indicator of airway inflammation, and is effort dependent. Other physiologic parameters require expensive machines and experienced operators to obtain reproducible results. Klein R., Fritz G. Yeung A., McQuade E., Mansell A. Spirometric Patterns in Childhood Asthma: Peak Flow Compared with Other Indices. Pediatr. Pulmonol., 1995, 20:372-379.
Endogenous production of nitrogen oxide in the human airway has been shown to be increased in patients with asthma and other inflammatory lung diseases. Gaston B., Drazen J., Chee, C., et al. Expired nitric oxide concentrations are elevated in patients with reactive airways disease. Endothelium. 1993; 1:S87; Gustafsson, I. E., Leone A. M., Persson M. G., Wiklund N. P., Moncada S., Endogenous nitric oxide is present in the exhaled air of rabbits, guinea pigs and humans. 1991; 181; 2:852-857. However, measurement of gas phase nitric oxide (nitrogen monoxide) per se in the parts per billion range found in the airway requires the use of mass spectrometry or chemiluminescent technology, which are cumbersome, expensive and not reasonably suited for home use.
Moreover, measurement of aqueous phase higher oxides of nitrogen compounds such as S-nitrosothiols, nitrite and nitrate, which are not nitrogen monoxide but which are likewise elevated in concentrations in subjects with inflammatory lung disease, has required that patients be hospitalized for invasive airway sampling procedures, including airway intubation and bronchoalveolar lavage. Gaston, B., Reilly J., Drazen J., et al., Endogenous nitrogen oxides and bronchodilator S-nitrosothiols in human airways. Proc. Natl. Acad. Sci., 1993; 90:10957-10961.